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      Optimised Anaesthesia to Reduce Post Operative Cognitive Decline (POCD) in Older Patients Undergoing Elective Surgery, a Randomised Controlled Trial

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          The study determined the one year incidence of post operative cognitive decline (POCD) and evaluated the effectiveness of an intra-operative anaesthetic intervention in reducing post-operative cognitive impairment in older adults (over 60 years of age) undergoing elective orthopaedic or abdominal surgery.

          Methods and Trial Design

          The design was a prospective cohort study with a nested randomised, controlled intervention trial, using intra-operative BiSpectral index and cerebral oxygen saturation monitoring to enable optimisation of anaesthesia depth and cerebral oxygen saturation in older adults undergoing surgery.


          In the 52 week prospective cohort study (192 surgical patients and 138 controls), mild (χ 2 = 17.9 p<0.0001), moderate (χ 2 = 7.8 p = 0.005) and severe (χ 2 = 5.1 p = 0.02) POCD were all significantly higher after 52 weeks in the surgical patients than among the age matched controls. In the nested RCT, 81 patients were randomized, 73 contributing to the data analysis (34 intervention, 39 control). In the intervention group mild POCD was significantly reduced at 1, 12 and 52 weeks (Fisher’s Exact Test p = 0.018, χ 2 = 5.1 p = 0.02 and χ 2 = 5.9 p = 0.015), and moderate POCD was reduced at 1 and 52 weeks (χ 2 = 4.4 p = 0·037 and χ 2 = 5.4 p = 0.02). In addition there was significant improvement in reaction time at all time-points (Vigilance Reaction Time MWU Z =  −2.1 p = 0.03, MWU Z = −2.7 p = 0.004, MWU Z = −3.0 p = 0.005), in MMSE at one and 52 weeks (MWU Z = −2.9 p = 0.003, MWU Z = −3.3 p = 0.001), and in executive function at 12 and 52 weeks (Trail Making MWU Z = −2.4 p = .0.018, MWU Z = −2.4 p = 0.019).


          POCD is common and persistent in older adults following surgery. The results of the nested RCT indicate the potential benefits of intra-operative monitoring of anaesthetic depth and cerebral oxygenation as a pragmatic intervention to reduce post-operative cognitive impairment.

          Trial Registration

          Controlled-Trials.com ISRCTN39503939

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          Most cited references 48

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          "Mini-mental state". A practical method for grading the cognitive state of patients for the clinician.

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            Mild cognitive impairment as a diagnostic entity.

            The concept of cognitive impairment intervening between normal ageing and very early dementia has been in the literature for many years. Recently, the construct of mild cognitive impairment (MCI) has been proposed to designate an early, but abnormal, state of cognitive impairment. MCI has generated a great deal of research from both clinical and research perspectives. Numerous epidemiological studies have documented the accelerated rate of progression to dementia and Alzheimer's disease (AD) in MCI subjects and certain predictor variables appear valid. However, there has been controversy regarding the precise definition of the concept and its implementation in various clinical settings. Clinical subtypes of MCI have been proposed to broaden the concept and include prodromal forms of a variety of dementias. It is suggested that the diagnosis of MCI can be made in a fashion similar to the clinical diagnoses of dementia and AD. An algorithm is presented to assist the clinician in identifying subjects and subclassifying them into the various types of MCI. By refining the criteria for MCI, clinical trials can be designed with appropriate inclusion and exclusion restrictions to allow for the investigation of therapeutics tailored for specific targets and populations.
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              Long-term consequences of postoperative cognitive dysfunction.

              Postoperative cognitive dysfunction (POCD) is common in elderly patients after noncardiac surgery, but the consequences are unknown. The authors' aim was to determine the effects of POCD on long-term prognosis. This was an observational study of Danish patients enrolled in two multicenter studies of POCD between November 1994 and October 2000. The cohort was followed up from the date of surgery until August 2007. Cognitive function was assessed by a neuropsychological test battery at three time points: before, at 1 week after, and at 3 months after noncardiac surgery. Data on survival, labor market attachment, and social transfer payments were obtained from administrative databases. The Cox proportional hazards regression model was used to compute relative risk estimates for mortality and disability, and the relative prevalence of time on social transfer payments was assessed by Poisson regression. A total of 701 patients were followed up for a median of 8.5 yr (interquartile range, 5.3-11.4 yr). POCD at 3 months, but not at 1 week, was associated with increased mortality (hazard ratio, 1.63 [95% confidence interval, 1.11-2.38]; P = 0.01, adjusted for sex, age, and cancer). The risk of leaving the labor market prematurely because of disability or voluntary early retirement was higher among patients with 1-week POCD (hazard ratio, 2.26 [1.24-4.12]; P = 0.01). Patients with POCD at 1 week received social transfer payments for a longer proportion of observation time (prevalence ratio, 1.45 [1.03-2.04]; P = 0.03). Cognitive dysfunction after noncardiac surgery was associated with increased mortality, risk of leaving the labor market prematurely, and dependency on social transfer payments.

                Author and article information

                Role: Editor
                PLoS One
                PLoS ONE
                PLoS ONE
                Public Library of Science (San Francisco, USA )
                15 June 2012
                : 7
                : 6
                [1 ]Wolfson Centre for Age-Related Diseases, King’s College London, London, United Kingdom
                [2 ]Department of Neurobiology, Ward and Society, Karolinska Institute, Stockholm, Sweden, Norway
                [3 ]Faculty of Science and Technology, Stavanger University Hospital, Stavanger, Norway
                [4 ]Institute of Ageing and Health, University of Newcastle, Newcastle, United Kingdom
                [5 ]Research Department of Primary Care and Population Health, University College London, London, United Kingdom
                [6 ]Research Directorate, Alzheimer’s Society (UK), London, United Kingdom
                [7 ]Centre for Human Psychopharmacology, Swinburne University, Melbourne, Australia
                [8 ]Department of Anaesthetics, King’s College Hospital, London, United Kingdom
                Massachusetts General Hospital, United States of America
                Author notes

                Conceived and designed the experiments: CB EJ DA BKS DL KW DG. Performed the experiments: EJ NG BKS DL JA DA NP BP DG. Analyzed the data: NG OBN EK. Contributed reagents/materials/analysis tools: BKS KW DG. Wrote the paper: CB EJ NG DA OBN BKS DL AC KW EK JA DA NP BP DG. Interpreting data: CB EJ NG AC DG. Literature search: CB EJ NG DA DL AC EK DG.

                Ballard et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
                Page count
                Pages: 9
                Research Article
                Cognitive Neuroscience
                Learning and Memory
                Anatomy and Physiology
                Physiological Processes
                Anesthesiology Monitoring
                Alzheimer Disease
                Cognitive Neurology
                Non-Clinical Medicine
                Health Care Policy
                Elderly Care



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